Regulated production of interferon-inducible T-cell chemoattractants by human intestinal epithelial cells

Gastroenterology. 2001 Jan;120(1):49-59. doi: 10.1053/gast.2001.20914.


Background & aims: Human intestinal epithelial cells inducibly express neutrophil and monocyte chemoattractants, yet little is known about the regulated production of T-cell chemoattractants by the intestinal epithelium. IP-10, Mig, and I-TAC are 3 CXC chemokines that are known to act as CD4(+) T-cell chemoattractants.

Methods: We studied constitutive chemokine expression in human colon, and defined the regulated expression of these chemokines by reverse-transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistology using cultured human intestinal epithelial cell lines and a novel adaptation of an in vivo human intestinal xenograft model.

Results: IP-10 and Mig were constitutively expressed by normal human colon epithelium, and their cognate receptor, CXCR3, was expressed by mucosal mononuclear cells. Interferon (IFN)-gamma stimulation increased mRNA expression and the polarized basolateral secretion of these chemokines by human colon epithelial cell lines; infection with enteroinvasive bacteria, or stimulation with the proinflammatory cytokines tumor necrosis factor alpha and interleukin 1alpha, strongly potentiated IFN-gamma-induced epithelial cell IP-10, Mig, and I-TAC production. Epithelial cell mRNA and protein expression of IP-10, Mig, and I-TAC were rapidly up-regulated in human intestinal xenografts in response to stimulation with IFN-gamma alone or in combination with IL-1.

Conclusions: The constitutive and regulated production of the IFN-gamma-inducible chemokines IP-10, Mig, and I-TAC by human intestinal epithelium, and the expression of their cognate receptor, CXCR3, by mucosal mononuclear cells, suggest that the intestinal epithelium can play a role in modulating physiologic and pathologic T cell-mediated mucosal inflammation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Bacterial Infections / immunology
  • Bacterial Infections / metabolism
  • CD4-Positive T-Lymphocytes / cytology*
  • CD4-Positive T-Lymphocytes / immunology
  • Chemokine CXCL10
  • Chemokine CXCL11
  • Chemokine CXCL9
  • Chemokines, CXC / genetics
  • Chemokines, CXC / metabolism*
  • Chemotaxis, Leukocyte / drug effects
  • Chemotaxis, Leukocyte / physiology*
  • Enteritis / immunology
  • Enteritis / metabolism
  • Fetal Tissue Transplantation
  • Fetus / cytology
  • Gene Expression / physiology
  • HT29 Cells
  • Humans
  • Intercellular Signaling Peptides and Proteins*
  • Interferon-gamma / pharmacology*
  • Interleukin-13 / metabolism
  • Interleukin-4 / metabolism
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, SCID
  • Neoplasm Transplantation
  • RNA, Messenger / analysis
  • Receptors, CXCR3
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / metabolism
  • Transplantation, Heterologous


  • Antineoplastic Agents
  • CXCL11 protein, human
  • CXCL9 protein, human
  • CXCR3 protein, human
  • Chemokine CXCL10
  • Chemokine CXCL11
  • Chemokine CXCL9
  • Chemokines, CXC
  • Cxcl11 protein, mouse
  • Cxcr3 protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-13
  • RNA, Messenger
  • Receptors, CXCR3
  • Receptors, Chemokine
  • Interleukin-4
  • Interferon-gamma